Characterization of the Relationship Between the Mesolimbic Reward System and Immune Functioning in Humans Via fMRI Neurofeedback
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 1
- 主要终点
- Immunological: change in anti HBs immunoglobins in plasma
研究概览
简要总结
The purpose of this study is to characterize the link between neurobehavioral measures of the mesolimbic reward system and immune functioning in healthy individuals, via fMRI neurofeedback modulation of mesolimbic reward system, and the consecutive assesment of immune response to Hepatitis B vaccination.
详细描述
For many years, the link between mental processes and physical health has remained obscure. Yet, over time, studies have begun to shed light on the intimate relationship between one's physical condition and mental state. One body of research aimed at elucidating the mind-body relationship is the study of the placebo effect. Placebo effects result mainly from conscious expectations to become healthy in therapeutic settings, and from unconscious conditioned responses to therapeutical settings that predict beneficial outcomes. Both processes are asociated with the neuronal reward system, which mediates reward processing, reward valuation and value based-learning. However, it remains unclear how do these processes mediated by the reward system promote therapeutic effects?
A recent study established a causal relationship between mesolimbic activation (VTA) and a measurable immunological response in mice. Stimulation of the VTA increased anti-bacterial immune functioning, an effect that was mediated by sympathetic nervous system, which is regulated by the brain and innervates all immune organs.
In light of these findings, the current study aims to assess the relationship between reward-related brain activation and immune functions in humans. fMRI Neurofeedback, a task that allows individuals to self modulate specified neural patterns in real-time, will be used to induce mesolimbic activation, following which healthy individuals will vaccinate against Hepatitis B. Immunological effects will be assessed by comparing immunological measures with respect to Hepatitis B prior and following mesolimbic activation and Hepatitis B vaccination.
The long-term goal of this study is to demonstrate a causal link between reward activation and an objective measurable physiological response of great significance, and to develop the means for individuals to exploit such mechanism for boosting immune functioning. i.e. to harness endogenous reward-related brain activation to strengthen the immune system, for clinical pathologies such as autoimmune diseases, maleble pathogens, cancer, etc.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Both participants and study personnel (Investigators and outcomes assessor) in the two active experimental arms (Mesolimbic NF and Control NF) will be blinded to group allocation.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants
- •Normal or corrected to normal vision
- •Compatibility with general MRI requirements
排除标准
- •History of neurological or psychiatric diseases that lead to hospitalization
- •Have received Hepatitis B vaccination in the last 10 years
- •Memory/cognitive neurological impairments
- •Chronic heart disease, diabities, high blood pressure, or autoimmune disease.
结局指标
主要结局
Immunological: change in anti HBs immunoglobins in plasma
时间窗: 6 weeks
To measure antibody titers in plasma, blood samples will be taken at four time points: before neurofeedback training (-14d); before Hepatitis B vaccination (day 0), 14 days and 28 days after vaccination. Anti-HBs change will be defined as average levels post-vaccination (14 and 28 days) minus average levels pre-vaccination (-14 and 0 days). \*19.09.22: due to extensive variability in baseline levels, anti-HB change will be defined as fold change between pre-and post-vaccination TPs, instead of absolute differences (blinding unharmed). The investigators predict that: i.Simple group effect: experimental arm subjects (mesolimbic fMRI NF) will exhibit higher levels of anti-HBs change than both the active comparator group (control fMRI-NF) and the no-treatment group. ii.Mesolimbic activation-Immunologic response correlation: mesolimbic activity during the neurofeedback task (across all NF participants) during the last session will predict anti-HBs levels following vaccination.
Immunological: change in cytokines blood concentrations following vaccination
时间窗: 17 days
To assess cytokine levels (e.g. IL-4, IL-6, TNFalpha, IFNgamma), the investigators will isolate peripheral blood mononuclear cells from the blood, and using flow cytometry analysis, characterize cytokine expression profile (initial intentions of using ELISA will be replaced due to quality tests (blinding unharmed) that showed poor signal, 28/12/21). As mere NF practice may affect cytokines levels, cytokines will be assessed in three time points - before NF training (-14d), before vaccination (day 0) and 3 days following vaccination. groupXtime (3X3) main effect and interactions will be inspected. The investigators predict that: i.Experimental arm group will exhibit higher levels of cytokines concentration that the active control group and natural history group. ii.Mesolimbic activation-Immunologic response correlation: mesolimbic activity during the neurofeedback task (across all NF participants) during the last session will predict changes in cytokines blood concentrations.
Reward Mesolimbic network (or control networks) BOLD activity during fMRI-NF task
时间窗: 1-3 weeks
ROIs of Mesolimbic reward network (or control networks) will be defined as mentioned in arms description \*see below. CSF voxels will be excluded from all ROIs. Outcome will be measured for each experimental group/control sub-group, as the contrast between regulation and watch conditions, for each NF run, each session (3\*4=12 runs). To assess differences in meoslimbic reward network activation between experimental and active control groups, a 12 by 2 (runXgroup) model will be constructed. \*23/8/22 to exploit superior offline processing, ROIs will be deifned via group instead of online individual subs analysis. The investigators predict that: i. Simple group effects during last (fourth) NF session: experimental arm subjects (mesolimbic fMRI NF) will exhibit higher meoslimbic reward network activity than the active comparator group. ii. Simple experimental arm group learning effects: a significant effect of run (time) for the experimental arm mesolimbic reward network acitivity.
次要结局
- Mental Strategies Questionnaire for NeuroFeedback (MSQ-NF)(6 weeks)
- Motivational tendencies based on K-means cluster analysis of questionnaires scores(6 week)
- Subjective reports of SHAPS (Snaith-Hamilton Pleasure Scale)(6 weeks)
- Subjective reports to Tridimensional Personality Questionnaire (TPQ)(6 weeks)
- Neurobehavioral measures of reward anticipation and responsivity during Monetary Incentive Delay (MID) task.(6 weeks)
- Behavioral measures of incentive motivation extracted from Effort Expenditure for Rewards Task (EEfRT).(6 weeks)
- long term immunological effects(3 months)
- Autonomic Nervous System (ANS) measure: Heart Rate Variability (HRV)(3 days - 4 weeks)
- Functional connectivity of mesolimbic network during rest fMRI scan(1-3 weeks)
- Subjective reports to Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ)(6 weeks)